The Serb is chasing a record-extending 11th Australian Open title and historic 25th Grand Slam crown.
“Whether I win or lose, I will always leave my heart out on the court. I’m just blessed to be making another record,” said Djokovic, 37, now coached by former rival Andy Murray.
Djokovic faces Czech 26th seed Tomas Machac next and is drawn to meet Spain’s Alcaraz in the last eight.
Four-time Grand Slam winner Alcaraz dropped just five games in an ominous display to sprint into the third round.
The third seed showed no mercy to Japan’s Yoshihito Nishioka in a 6-0, 6-1, 6-4 rout in 81 minutes.
“The less time you spend on court in the Grand Slams, especially in the beginning, it is going to be better,” said Alcaraz, who is yet to go beyond the quarter-finals in Melbourne.
Second seed Zverev swept through with a straight-sets victory over Spain’s Pedro Martinez.
Heading home on Wednesday with Ruud was qualifier Hady Habib, who on Sunday became the first player from Lebanon to win a Grand Slam match.
He exited in three sets to France’s Ugo Humbert.
Olympic champion Zheng was sent packing 7-6 (7/3), 6-3 by world number 97 Laura Siegemund, the second-oldest player in the women’s draw at age 36.
“I knew I just had to play more than my best tennis. I had nothing to lose so I just told myself to swing free,” said the German.
“It’s tennis. Nothing more,” said China’s Zheng, 22, who was given two time violations and lost her cool as her tilt at a maiden major crown evaporated in only the second round.
Sabalenka dropped her serve three times and faced 11 break points before overcoming Spain’s Jessica Bouzas Maneiro 6-3, 7-5, rattling off the last five games in a row.
“I have to fight. Today’s match proved that. Girls can go there and just play without any fear, without anything to lose. They can put you in really uncomfortable positions,” said Sabalenka, who beat Zheng in the 2024 final.
The win kept the Belarusian world number one on course for a rare hat-trick of consecutive Australian Open titles, a feat last achieved 26 years ago by Martina Hingis and only matched by four other women in history.
Former world number one Osaka, the 2019 and 2021 champion in Australia but now unseeded, stormed back to defeat 20th seed Karolina Muchova 1-6, 6-1, 6-3.
Osaka called it a “little revenge” for defeat at the US Open in August to the Czech.
World number three Gauff, who finished 2024 by winning the China Open and the WTA Tour Finals, fought back from 5-3 down in the second set to see off Britain’s Jodie Burrage 6-3, 7-5.
Asked what she had to do to beat 30th seed Leylah Fernandez next, Gauff told reporters: “Obviously serve better!”
Gauff’s fellow American Jessica Pegula, beaten in the US Open final by Sabalenka last year, eased through against Belgium’s Elise Mertens.
On Thursday, men’s number one Jannik Sinner steps up the defence of his Melbourne crown when he faces Australian wildcard Tristan Schoolkate.
Daniil Medvedev, Iga Swiatek and Brazilian teenage sensation Joao Fonseca are also in second-round action.
